Characterization of left-handed beta helix-domains, and identification and functional annotation of proteins...

Only about 0.3% of the entries in UniProt database have manually curated annotation. Annotation at the molecular level often relies on low-throughput one-protein-at-a-time approach. Computational methods bridge this gap by assigning function based on sequence and/or fold similarity. Left-handed beta helix (LbH) consists of three repeating six-stranded beta-strands forming an 18-mer turn of the helix. Analysis of LbH-domains showed that variations are found in the number of residues in a beta-strand (5-7, 6 being the most common), number of turns (4-10) of the helix, insertions of one or more loops of variable length (0-36 residues), and the location of loop insertion. An 18-mer HMM profile was created which identifies LbH-domain containing proteins using sequence as the only input; the number of false positives is zero when proteins tested were those with known 3D structures. 136 474 entries of TrEMBL database were found to contain LbH-domain. Rules developed by analyzing LbH-domain containing acyltransferases, gamma-class carbonic anhydrases, and nucleotidyltransferases have led to the annotation of 17 389 TrEMBL entries which currently have no functional tag.